Acute respiratory distress syndrome, ARDS, afflicts about 200,000 Americans each year. The pathology consists of rapid onset of respiratory symptoms including radiographic bilateral opacities and pulmonary edema. The primary risk factors for the development of ARDS are pneumonia, aspiration, major trauma, sepsis, and inhalation injury. Despite the adoption of lung-protective-ventilation, the mortality rate remains about 30-40%. Common to all patients with ARDS is abnormal and sustained degradation of surfactant. The addition of repeated aerosol surfactant replacement therapy is hypothesized to reduce surface tension in the airways and alveoli. This decreases the transpulmonary pressure required to open atelectatic airways and collapsed alveoli with a resultant increase in respiratory capacity, improved gas exchange and the consequent resolution of the hypoxemia together with improved CO2 removal. Patients with ARDS related to a direct insult (e.g. pneumonia, aspiration) could most benefit from surfactant replacement therapy administered early in the course of the clinical syndrome when inflammation is present but prior to the onset of severe lung dysfunction. We propose to develop, manufacture and test alpha versions of SUPRAER- Clinic that, for the first time, enables the treatment of mild, early stage ARDS patients with clinically relevant doses of fine particle aerosols of surfactant prior to the need for these patients to be intubated. SUPRAER-Clinic aerosolizes a viscous surfactant suspension, evaporates water from the aerosol and concentrates this solid phase aerosol prior to its delivery. SUPRAER-Clinic is designed to efficiently and rapidly deliver high doses of these fine particle aerosols to patients with compromised lung function in a clinical setting. SUPRAER-Clinic has the provision for positive pressure respiratory assist to improve peripheral lung deposition of surfactant aerosols in these patients with heterogeneously impaired respiratory function. The development of SUPRAER-Clinic for surfactant will open up the potential for SUPRAER-Clinic to deliver other agents to the lungs, especially those that comprise highly viscosity fluids that are recalcitrant to aerosol delivery by other methods. !